The various subunits of the plasma membrane bound reaction responsible for the production of eNOS derived nitric oxide (NO). This reaction can uncouple and be a net producer of [O2']. In diabetes there are several reasons for uncoupling. Decreased or dysfunctional eNOS enzyme, substrate L-arginine, deficient or dysfunctional cofactor BH4. Increased ROS, RNS, glucose, native LDL-C and oxidized mmLDL-C, ADMA, Hcy, and CRP. Each of these factors can contribute to making the endothelium of the patient with MS, IR, PD and overt T2DM a net producer of [O2']. The above dysfunctional endothelium with a decreased ratio of NO / ROS. RNS can further contribute to the overall increase in intimal redox stress and atheroscleropathy.